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Combined pharmacotherapy that increases proliferation and decreases apoptosis optimally enhances intestinal adaptation.
J Pediatr Surg. 2006 Apr; 41(4):719-24; discussion 719-24.JP

Abstract

BACKGROUND

Adaptation after massive small bowel resection (SBR) is associated with increased rates of enterocyte proliferation (P) and apoptosis (A). In the present study, we sought to determine the effect of dual therapy designed to increase P and simultaneously reduce A.

METHODS

C57Bl/6 mice underwent a 50% small bowel resection (SBR) or sham operation, and then received an inhibitor of apoptosis (pan-caspase inhibitor), a stimulus for proliferation (epidermal growth factor; EGF), a combination, or vehicle control. After 3 days, adaptive morphology (villus height, crypt depth) and rates of enterocyte turnover (proliferation and apoptosis) were measured in the remnant ileum.

RESULTS

Adaptation in controls and treated with the inhibitor was similar. EGF-treated mice demonstrated an even greater adaptive response. Combined therapy with the inhibitor and EGF resulted in maximal adaptation as gauged by the greatest increases in villus height and crypt depth and ratio of rates of P to A.

CONCLUSION

The capacity for adaptation following massive SBR is maintained via tight regulation of cell production and death. Pharmacologic intervention directed at increasing enterocyte proliferation while simultaneously decreasing apoptosis augments adaptation greater than either intervention alone and may provide a useful strategy to clinically amplify adaptation.

Authors+Show Affiliations

Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16567183

Citation

Bernal, Nicole P., et al. "Combined Pharmacotherapy That Increases Proliferation and Decreases Apoptosis Optimally Enhances Intestinal Adaptation." Journal of Pediatric Surgery, vol. 41, no. 4, 2006, pp. 719-24; discussion 719-24.
Bernal NP, Stehr W, Profitt S, et al. Combined pharmacotherapy that increases proliferation and decreases apoptosis optimally enhances intestinal adaptation. J Pediatr Surg. 2006;41(4):719-24; discussion 719-24.
Bernal, N. P., Stehr, W., Profitt, S., Erwin, C. R., & Warner, B. W. (2006). Combined pharmacotherapy that increases proliferation and decreases apoptosis optimally enhances intestinal adaptation. Journal of Pediatric Surgery, 41(4), 719-24; discussion 719-24.
Bernal NP, et al. Combined Pharmacotherapy That Increases Proliferation and Decreases Apoptosis Optimally Enhances Intestinal Adaptation. J Pediatr Surg. 2006;41(4):719-24; discussion 719-24. PubMed PMID: 16567183.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined pharmacotherapy that increases proliferation and decreases apoptosis optimally enhances intestinal adaptation. AU - Bernal,Nicole P, AU - Stehr,Wolfgang, AU - Profitt,Sherri, AU - Erwin,Christopher R, AU - Warner,Brad W, PY - 2006/3/29/pubmed PY - 2006/10/27/medline PY - 2006/3/29/entrez SP - 719-24; discussion 719-24 JF - Journal of pediatric surgery JO - J Pediatr Surg VL - 41 IS - 4 N2 - BACKGROUND: Adaptation after massive small bowel resection (SBR) is associated with increased rates of enterocyte proliferation (P) and apoptosis (A). In the present study, we sought to determine the effect of dual therapy designed to increase P and simultaneously reduce A. METHODS: C57Bl/6 mice underwent a 50% small bowel resection (SBR) or sham operation, and then received an inhibitor of apoptosis (pan-caspase inhibitor), a stimulus for proliferation (epidermal growth factor; EGF), a combination, or vehicle control. After 3 days, adaptive morphology (villus height, crypt depth) and rates of enterocyte turnover (proliferation and apoptosis) were measured in the remnant ileum. RESULTS: Adaptation in controls and treated with the inhibitor was similar. EGF-treated mice demonstrated an even greater adaptive response. Combined therapy with the inhibitor and EGF resulted in maximal adaptation as gauged by the greatest increases in villus height and crypt depth and ratio of rates of P to A. CONCLUSION: The capacity for adaptation following massive SBR is maintained via tight regulation of cell production and death. Pharmacologic intervention directed at increasing enterocyte proliferation while simultaneously decreasing apoptosis augments adaptation greater than either intervention alone and may provide a useful strategy to clinically amplify adaptation. SN - 1531-5037 UR - https://www.unboundmedicine.com/medline/citation/16567183/Combined_pharmacotherapy_that_increases_proliferation_and_decreases_apoptosis_optimally_enhances_intestinal_adaptation_ DB - PRIME DP - Unbound Medicine ER -